A significant number of human neonates are smaller than normal at birth. These infants are less healthy and have a higher mortality than neonates of normal weight. Information on hormones that regulate growth of fetuses is sparse and contradictory, and virtually nothing is known about possible hormonal effects on the growth of mammalian embryos in utero. Meaningful information on these subjects may allow the incidence of human fetal growth retardation to be reduced. We will investigate the hormones that are required for growth and differentiation of rats during the embryonic, fetal and neonatal periods using new techniques that we have developed. One of these involves transplanting whole early embryos, or fetal paws under the kidney capsule of juvenile or adult syngeneic rats. At this site transplanted tissue grows well and differentiates normally. Our previous work indicates that growth of fetal rat tissues requires insulin (I) and somatomedins (SM). We will investigate when embryonic tissue develops a dependence on these hormones by transplanting embryos into hosts that are either diabetic (D) or hypophysectomized (HX). The latter are SM deficient. We have also shown that sometime after birth the tissues of the rat become dependent on thyroid hormones (TH), and growth hormone (GH) for growth. We will investigate when this dependence emerges by transplanting xiphoid cartilage from neonatal rats under the kidney capsule of month-old host rats which are intact, HX or thyroidectomized (TX). A divergence in the growth curves of the transplants in the TX and HX hosts will indicate when they became dependent on GH (or SM) and TH, respectively. The direct effects in vivo of growth promoting hormones (I, SM, TH and GH) on growth of transplanted tissue from embryos, fetuses and neonates will be investigated using a new infusion procedure. The tissues are transplanted under the capsule of both kidneys of host rats which are either HX or D. The artery to one kidney is cannulated and hormone solutions are infused into the cannulated renal artery via an osmotic minipump. Thus the transplants on the infused kidney are exposed to direct effects of the hormone while the transplants on the contralateral kidney are unaffected. We will also test the direct growth promoting effects of hormones in juvenile and adult rats that are HX or D by infusing solutions into the right femoral artery. Growth of the tissues on the right leg is compared to that in the left (uninfused) leg. The possibility that infusing GH into one leg of HX rats will cause production of SM will also be investigated.